HIV controllers

On 12.12 I heard a talk by Bruce Walker of Partners AIDS Research Centre, Massachusetts General Hospital, with the title ‘Prospects for an AIDS vaccine’. He started by saying that, given the difficulties which have been experienced in trying to develop a vaccine which could actually prevent or cure AIDS, another strategy which should be considered is to develop a vaccine which would bring people infected with HIV into a state where they could maintain a constant low viral load (and thus a symptom-free state) without medication. A fact which suggests that this might be possible is the existence of ‘HIV controllers’, people who can do this spontaneously. That is to say, although infected with HIV they can maintain very low viral loads for very long times (perhaps indefinitely) without needing drugs. Within the class of controllers there is a special type, the ‘elite controllers’ where the virus load is undetectable with available techniques. If it was known what is special about controllers or elite controllers this might provide the basis for developing the desired vaccine. There is a project to do tests on these controllers to try to find out what is going on. More information can be found on the web page http://www.hivcontrollers.org/.

What has been discovered so far? One of the problems in fighting HIV is that the virus evolves very fast to produce different quasispecies which can evade any tool being used to combat the virus. It appears that those variants of the virus found in controllers are different from those found in the general population of individuals infected with HIV. The viruses in controllers are less fit. Moreover it seems that this is not due to these people having been infected by less fit viruses – rather they have evolved to become less fit in these patients. When HIV evolves to escape attacks by the immune system or drugs it is moving in a vast genetic landscape. It seems that in controllers the direction of this evolution is biased and it ends up in regions of lower
fitness. But what is it that creates this bias? There has been a large scale genetic analysis of SNPs (single nucleotide polymorphisms) in contollers to look for special genetic characters. This gave a strong indication that a region of the genome which is involved is the HLA (human lymphocyte antigen) region. This suggests a direct involvement of the immune system and in particular of the MHC molecules (major histocompatibility complex) which are coded for by HLA genes. There are also signs that cytotoxic T-cells (CD8+) have an important role to play. The project continues. It represents a hope that an AIDS vaccine can finally be developed and, perhaps, a useful new strategy for developing vaccines for other ‘difficult’ diseases.

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